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PERSPECTIVE

Genetic interaction screens advance in reverse

¹ Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA; ² Harvard Biophysics Graduate Program, Harvard Medical School, Boston, Massachusetts 02115, USA; ³ Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA; ⁴ Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA

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A genetic interaction is defined by the emergence of a surprising phenotype when two genes are disrupted together. In 2004, Baetz et al. (2004) reported a new kind of large-scale reverse-genetic screen for genetic interactions. By mating a haploid yeast strain carrying a "query mutation" to many haploid strains—each carrying a single engineered mutation at a second (unlinked) locus—they efficiently produced diploid strains carrying two heterozygous mutations. If the double-mutant strain shows reduced fitness relative to each single-mutant strain, this indicates a genetic interaction traditionally called "unlinked noncomplementation" (UNC). UNC interactions have been noted to frequently occur between genes that . . . [Full Text of this Article]

	Gene dosage and poison models to explain UNC relationships

 

	The trouble with forward genetics

 

	The awesome power of reverse genetics

 

	Reverse-genetic interactions

 

	Reverse-genetic approaches to gene dosage effects

 

	Functional divergence among pairs of paralogous ribosomal protein genes

 

	Future directions

 

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